This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Our lab (Hoeft et al, 2007) recently used fMRI to image participants with fragile X syndrome as they performed the Go/Nogo task. In contrast to the robust, right-lateralized fronto-striatal circuit active in typically developing participants during the Nogo portion of the task, we found reduced activation in this same circuit in the fragile X group. Specific Aims: In the present study, we wanted to assess whole-brain functional connectivity (psychophysiological interaction;PPI) analyses using the previously imaged group of 10 male adolescents with fragile X as well as 10 matched typically-developing controls and a third group of age-matched, developmentally-delayed control participants. The goal of this study was to determine whether the caudate specifically showed abnormal functional connectivity with the frontal cortex in participants with fragile X. Methods: To test this, we performed psychophysiological interaction (PPI) functional connectivity analyses using right and left caudate head and bodies as seed regions-of-interest (ROIs;right and left, ROI of interest and control ROI, respectively). Time-series were extracted from suprathreshold voxels within anatomically defined ROIs for each subject and were convolved with the effects of interest (Nogo vs. Go epochs), and used as regressors in the general linear model (GLM).